Secreted frizzled-related proteins (Sfrps) are classified as Wnt antagonists, but recent studies have shown that some Sfrps can positively modulate Wnt signalling. Is this a general property of all Sfrps and, if so, how do Sfrps regulate Wnt signalling? Here, Paola Bovolenta and colleagues (see ) show that Sfrp1 and Sfrp2 positively regulate Wnt signalling, and are required for Wnt-mediated development of the mouse optic cup. The researchers show that specification of the peripheral optic cup (OCP), which is known to be dependent on Wnt signalling, is grossly defective in mice lacking both Sfrp1 and Sfrp2. In these mutants, Wnt spreading across the OCP is impaired, suggesting that Sfrps can influence the diffusion of Wnts. In support of this, the researchers demonstrate that Sfrp1 overexpression flattens the gradient of Wingless (a Drosophila Wnt homologue) across the Drosophila imaginal disc. These studies highlight a new and unexpected role for Sfrps in regulating the levels and distribution of Wnts during development.
